Improving Bioavailability & Solubility: Each Molecule Is Unique

The virtual 2020 Global Drug Bioavailability Enhancement Summit this past December showcased novel technologies and platforms aimed at addressing bioavailability and solubility challenges. These included techniques like elec­trospinning, mesoporous silica technology, physiochemical optimization, amorphous nanoparticle engineering, and pharmacokinetic modeling. And the end goal is the same: Save time and money while accelerating formulation devel­opment.

Proprietary Technologies for Amphiphilic Molecules

Some biologics require high con­centrations to be effective, even though they may be soluble. Formu­lating at these high concentrations can lead to issues with solubility or viscos­ity, requiring advanced delivery tech­nologies such as the formulation of nanoparticles or microparticles. These engineered particles flow well even at high concentrations.

Formulation strategy is deter­mined by looking at the physicochem­ical characteristics of a given active pharmaceutical ingredient (API). For crystalline API compounds with high melting points, a go-to technology for Lubrizol Life Science Health (LLS Health) is nanomilling, which reduces the size and increases the dissolution rate.

“Depending on lipid solubility, nanoemulsions or our proprietary LyoCell® technology can be useful ap­proaches,” says Dr. Robert Lee, Presi­dent, LLS Health, CDMO Division. “Ly­oCells are better able to accommodate amphiphilic molecules (i.e., those with both a hydrophilic and a hydrophobic region) and are compatible with both small molecules and biologics.”

Assessing the feasibility of nanomilling provides clients with a cost-effective and efficient way to de­termine whether particle size reduction will work for their API, he continues. Nanomilling is well suited for formu­lating APIs with poor aqueous solubil­ity and has been used in a range of dosage forms, including liquids, capsules, tablets, and injectables. “Be­cause this process is in an aqueous vehicle, it bypasses the problems as­sociated with the large volumes and flammability of organic solvents used in other methods; it is also scalable and commercially validated,” he says.

Nanomilled API particles — nanoparticles — can be formulated as liquids, lyophilized powders, or oral solid dosage forms. Solid-lipid nanoparticles (SLNs) are submicron lipid particles that are used as an API delivery vehicle, including for hy­drophobic and high molecular weight APIs. “Their cost and recognized safety make them an attractive alternative,” says Dr. Lee.

Polymeric nanoparticles are a rel­atively new addition to the solubility arsenal and have been used with serum albumin to make such drugs as Abraxane®. Additionally, other partic­ulate systems comprised of inorganic compounds — silica, magnetite, gold — in a formulation matrix or coating that incorporates chemotherapeutics or other APIs can improve bioavail­ability.

LLS Health has also developed SATx technology, an interpretation of antibody-drug conjugates in which the surface of a nanoparticle loaded with a chemotherapeutic agent is deco­rated with biologics or targeting molecules, such as monoclonal anti­bodies. The SATx technology has been successfully applied to vaccines, says Dr. Lee.”

Learn how LLS Health’s Proprietary Technologies can solve your next formulation challenge. 

Read the full article at Drug Development and Delivery.